Glucose and insulin response to conditioned feeding in lean and genetically obese hyperglycemic (ob/ob) mice

The study reported here investigated the role of neuroendocrine reflexes in the stimulation of insulin secretion associated with feeding in lean and genetically obese hyperglycemic (ob/ob) mice. Twenty-week-old mice were conditioned over four weeks to restricted feeding periods of consecutively seven, four and two hours a day. Basal plasma glucose concentrations before feeding were raised in conditioned lean mice but lowered in conditioned ob/ob mice, with normalization of glycemia in ob/ob mice by four weeks. Conditioned mice consumed more food during the feeding period than control mice prefasted for the same time. Although the quantity of food consumed was less than the normal 24-hour intake of age-matched mice fed ad libitum, body weights were well maintained, indicating adaptations of metabolic efficiency or energy expenditure or both. During the feeding period, conditioned mice displayed a markedly enhanced plasma insulin response accompanied by a smaller increase in plasma glucose despite the consumption of more food. An anticipatory rise in plasma insulin was not evident when food was withheld during the prescribed two-hour feeding period after four weeks of conditioning. The results demonstrate that basal glucose concentrations were normalized in ob/ob mice but raised in lean mice by the restricted conditioned feeding procedure. Basal insulin concentrations and body weights were not significantly altered, but conditioning to expect food augmented the insulin response initiated by feeding in both lean and ob/ob mice.